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Journal of Zhejiang University SCIENCE B 2022 Vol.23 No.12 P.975-988


Circular RNAs: typical biomarkers for bone-related diseases

Author(s):  Linghui HU, Wei WU, Jun ZOU

Affiliation(s):  School of Exercise and Health, Shanghai University of Sport, Shanghai 200438, China

Corresponding email(s):   junzou@sus.edu.cn

Key Words:  Circular RNA, Bone-related disease, Competing endogenous RNA (ceRNA), MicroRNA

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Linghui HU, Wei WU, Jun ZOU. Circular RNAs: typical biomarkers for bone-related diseases[J]. Journal of Zhejiang University Science B, 2022, 23(12): 975-988.

@article{title="Circular RNAs: typical biomarkers for bone-related diseases",
author="Linghui HU, Wei WU, Jun ZOU",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Circular RNAs: typical biomarkers for bone-related diseases
%A Linghui HU
%A Wei WU
%A Jun ZOU
%J Journal of Zhejiang University SCIENCE B
%V 23
%N 12
%P 975-988
%@ 1673-1581
%D 2022
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2200211

T1 - Circular RNAs: typical biomarkers for bone-related diseases
A1 - Linghui HU
A1 - Wei WU
A1 - Jun ZOU
J0 - Journal of Zhejiang University Science B
VL - 23
IS - 12
SP - 975
EP - 988
%@ 1673-1581
Y1 - 2022
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2200211

Bone is a connective tissue that has important functions in the human body. Cells and the extracellular matrix (ECM) are key components of bone and are closely related to bone-related diseases. However, the outcomes of conventional treatments for bone-related diseases are not promising, and hence it is necessary to elucidate the exact regulatory mechanisms of bone-related diseases and identify novel biomarkers for diagnosis and therapy. circular RNAs (circRNAs) are single-stranded RNAs that form closed circular structures without a 5' cap or 3' tail and polycyclic adenylate tails. Due to their high stability, circRNAs have the potential to be typical biomarkers. Accumulating evidence suggests that circRNAs are involved in bone-related diseases, including osteoarthritis, osteoporosis, osteosarcoma, multiple myeloma, intervertebral disc degeneration, and rheumatoid arthritis. Herein, we summarize the recent research progress on the characteristics and functions of circRNAs, and highlight the regulatory mechanism of circRNAs in bone-related diseases.


概要:骨是一种在人体中具有重要功能的结缔组织。细胞和细胞外基质(Extracellular matrix,ECM)是骨骼的关键组成部分,与骨相关疾病密切相关。然而,常规方法治疗骨相关疾病的结果并不乐观,因此需要通过阐明骨相关疾病的确切调控机制,寻找用于疾病诊断和治疗的新型生物标志物。环状RNA(Circular RNA,circRNA)是一种具有闭合环状结构的没有5’端或3’端多环腺苷酸尾的单链RNA。由于其高稳定性,circRNA有望成为典型的生物标志物。并且越来越多的证据表明circRNA参与调控骨相关疾病,包括骨关节炎、骨质疏松、骨肉瘤、多发性骨髓瘤、椎间盘退变和类风湿关节炎。本文综述了近年来circRNA特性和功能的研究进展,重点阐述了circRNA在骨相关疾病中的调控机制。


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]AnsariN, SimsNA, 2020. The cells of bone and their interactions. In: Stern PH (Ed.), Bone Regulators and Osteoporosis Therapy. Springer, Cham, p.1-25.

[2]BaiZM, KangMM, ZhouXF, et al., 2020. CircTMBIM6 promotes osteoarthritis-induced chondrocyte extracellular matrix degradation via miR-27a/MMP13 axis. Eur Rev Med Pharmacol Sci, 24(15):7927-7936.

[3]BlankM, SimsNA, 2019. Cellular processes by which osteoblasts and osteocytes control bone mineral deposition and maturation revealed by stage-specific EphrinB2 knockdown. Curr Osteoporos Rep, 17(5):270-280.

[4]BombardieriM, KamNW, BrentanoF, et al., 2011. A BAFF/APRIL-dependent TLR3-stimulated pathway enhances the capacity of rheumatoid synovial fibroblasts to induce AID expression and Ig class-switching in B cells. Ann Rheum Dis, 70(10):1857-1865.

[5]BuckDW II, DumanianGA, 2012. Bone biology and physiology: Part I. The fundamentals. Plast Reconstr Surg, 129(6):1314-1320.

[6]CaiYJ, LiangRG, XiaoSB, et al., 2021. Circ_0088194 promotes the invasion and migration of rheumatoid arthritis fibroblast-like synoviocytes via the miR-766-3p/MMP2 axis. Front Immunol, 12:628654.

[7]ChangHZ, WangHZ, YangXL, et al., 2021. Comprehensive profile analysis of differentially expressed circRNAs in glucose deprivation-induced human nucleus pulposus cell degeneration. Biomed Res Int, 2021:4770792.

[8]CharlierE, RelicB, DeroyerC, et al., 2016. Insights on molecular mechanisms of chondrocytes death in osteoarthritis. Int J Mol Sci, 17(12):2146.

[9]ChenCJ, YinP, HuSX, et al., 2020. Circular RNA-9119 protects IL-‍1β‍-treated chondrocytes from apoptosis in an osteoarthritis cell model by intercepting the microRNA-26a/PTEN axis. Life Sci, 256:117924.

[10]ChenF, WangXH, FuS, et al., 2020a. Circular RNA circ-CDYL sponges miR-1180 to elevate yes-associated protein in multiple myeloma. Exp Biol Med, 245(11):‍925-932.

[11]ChenF, WangXH, FuS, et al., 2020b. Effect of the up-regulation of circular RNA hsa_circ_0069767 derived from C-KIT on the biological behavior of multiple myeloma cells. Cancer Manag Res, 12:11321-11331.

[12]ChenI, ChenCY, ChuangTJ, 2015. Biogenesis, identification, and function of exonic circular RNAs. WIREs RNA, 6(5):563-579.

[13]ChenLL, 2016. The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol, 17(4):205-211.

[14]ChenQ, LiuT, BaoY, et al., 2020. CircRNA cRAPGEF5 inhibits the growth and metastasis of renal cell carcinoma via the miR-27a-3p/TXNIP pathway. Cancer Lett, 469:68-77.

[15]ChenSF, YaoYN, LuS, et al., 2020. CircRNA0001859, a new diagnostic and prognostic biomarkers for COPD and AECOPD. BMC Pulm Med, 20:311.

[16]ChenX, OuyangZX, ShenY, et al., 2019. CircRNA_28313/miR-‍195a/CSF1 axis modulates osteoclast differentiation to affect OVX-induced bone absorption in mice. RNA Biol, 16(9):1249-1262.

[17]ChenYX, ZhangSC, BaiCQ, et al., 2020. Circ_0000885 enhances osteosarcoma progression by increasing FGFR1 expression via sponging miR-1294. Cancer Manag Res, 12:6441-6452.

[18]ChenZH, ZhangWB, DengM, et al., 2020. CircGLCE alleviates intervertebral disc degeneration by regulating apoptosis and matrix degradation through the targeting of miR-587/STAP1. Aging, 12(21):21971-21991.

[19]ChengXF, ZhangL, ZhangK, et al., 2018. Circular RNA VMA21 protects against intervertebral disc degeneration through targeting miR-200c and X linked inhibitor-of-apoptosis protein. Ann Rheum Dis, 77(5):770-779.

[20]ConnVM, HugouvieuxV, NayakA, et al., 2017. A circRNA from SEPALLATA3 regulates splicing of its cognate mRNA through R-loop formation. Nat Plants, 3:17053.

[21]CoughlanT, DockeryF, 2014. Osteoporosis and fracture risk in older people. Clin Med, 14(2):187-191.

[22]CuiSQ, ZhangL, 2020. circ_001653 silencing promotes the proliferation and ECM synthesis of NPCs in IDD by downregulating miR-486-3p-mediated CEMIP. Mol Ther Nucl Acids, 20:385-399.

[23]DavidJP, SchettG, 2010. TNF and bone. Curr Dir Autoimmun, 11:135-144.

[24]del FattoreA, TetiA, RucciN, 2012. Bone cells and the mechanisms of bone remodelling. Front Biosci, 4(6):2302-2321.

[25]DischerDE, MooneyDJ, ZandstraPW, 2009. Growth factors, matrices, and forces combine and control stem cells. Science, 324(5935):1673-1677.

[26]DongL, QuFF, 2020. CircUBAP2 promotes SEMA6D expression to enhance the cisplatin resistance in osteosarcoma through sponging miR-506-3p by activating Wnt/β‍-catenin signaling pathway. J Mol Histol, 51(4):‍‍329-340.

[27]FangW, MuJ, YangY, et al., 2021. CircRERE confers the resistance of multiple myeloma to bortezomib depending on the regulation of CD47 by exerting the sponge effect on miR-152-3p. J Bone Oncol, 30:100381.

[28]FengYS, ZhangL, WuJY, et al., 2019. CircRNA circ_0000190 inhibits the progression of multiple myeloma through modulating miR-767-5p/MAPK4 pathway. J Exp Clin Cancer Res, 38:54.

[29]Florencio-SilvaR, da Silva SassoGR, Sasso-CerriE, et al., 2015. Biology of bone tissue: structure, function, and factors that influence bone cells. Biomed Res Int, 2015:421746.

[30]FuYF, LiuX, ZhangFR, et al., 2019. Bortezomib-inducible long non-coding RNA myocardial infarction associated transcript is an oncogene in multiple myeloma that suppresses miR-29b. Cell Death Discov, 10(4):319.

[31]GaoM, LiCY, XiaoH, et al., 2019. hsa_circ_0007841: a novel potential biomarker and drug resistance for multiple myeloma. Front Oncol, 9:1261.

[32]GengXC, JiaYC, ZhangYH, et al., 2020. Circular RNA: biogenesis, degradation, functions and potential roles in mediating resistance to anticarcinogens. Epigenomics, 12(3):267-283.

[33]Gonzalez-SantamartaM, QuinetG, Reyes-GarauD, et al., 2020. Resistance to the proteasome inhibitors: lessons from multiple myeloma and mantle cell lymphoma. In: Barrio R, Sutherland JD, Rodriguez MS (Eds.), Proteostasis and Disease: From Basic Mechanisms to Clinics. Springer, Cham, p.153-174.

[34]GuanJX, GanL, JinD, et al., 2021. Overexpression of circ_0021739 in peripheral blood mononuclear cells in women with postmenopausal osteoporosis is associated with reduced expression of microRNA-194-5p in osteoclasts. Med Sci Monit, 27:e929170.

[35]GuarnerioJ, BezziM, JeongJC, et al., 2016. Oncogenic role of fusion-CircRNAs derived from cancer-associated chromosomal translocations. Cell, 166(4):1055-1056.

[36]GuoJU, AgarwalV, GuoHL, et al., 2014. Expanded identification and characterization of mammalian circular RNAs. Genome Biol, 15(7):409.

[37]GuoW, MuK, ZhangB, et al., 2020a. The circular RNA FAM169A functions as a competitive endogenous RNA and regulates intervertebral disc degeneration by targeting miR-583 and BTRC. Cell Death Discov, 11(5):315.

[38]GuoW, MuK, ZhangB, et al., 2020b. The circular RNA circ-GRB10 participates in the molecular circuitry inhibiting human intervertebral disc degeneration. Cell Death Discov, 11(8):612.

[39]HoldtLM, StahringerA, SassK, et al., 2016. Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans. Nat Commun, 7:12429.

[40]HsiaoKY, SunHS, TsaiSJ, 2017. Circular RNA‍–‍new member of noncoding RNA with novel functions. Exp Biol Med, 242(11):1136-1141.

[41]HuangGQ, LiangM, LiuHY, et al., 2020. CircRNA hsa_ circRNA_104348 promotes hepatocellular carcinoma progression through modulating miR-187-3p/RTKN2 axis and activating Wnt/β-catenin pathway. Cell Death Discov, 11(12):1065.

[42]HuangH, WuHW, HuYX, 2020. Current advances in chimeric antigen receptor T-cell therapy for refractory/relapsed multiple myeloma. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(1):29-41.

[43]HuangS, YangB, ChenBJ, et al., 2017. The emerging role of circular RNAs in transcriptome regulation. Genomics, 109(5-6):401-407.

[44]HuangXQ, CenX, ZhangB, et al., 2019. Prospect of circular RNA in osteogenesis: a novel orchestrator of signaling pathways. J Cell Physiol, 234(12):21450-21459.

[45]HuangYX, XiaoD, HuangSH, et al., 2020. Circular RNA YAP1 attenuates osteoporosis through up-regulation of YAP1 and activation of Wnt/β‍-catenin pathway. Biomed Pharmacother, 129:110365.

[46]HuangYZ, GaoJ, WangJL, et al., 2021. Inhibition of intervertebral disc disease progression via the circPKNOX1–miR-370-3p–KIAA0355 axis. Cell Death Discov, 7:39.

[47]HuangZH, MaWM, XiaoJH, et al., 2021. CircRNA_0092516 regulates chondrocyte proliferation and apoptosis in osteoarthritis through the miR-337-3p/PTEN axis. J Biochem, 169(4):467-475.

[48]HuangZY, YuanCY, GuHJ, et al., 2020. Circular RNA circHIPK3 promotes cell metastasis through miR-637/STAT3 axis in osteosarcoma. Biomed Res Int, 2020:2727060.

[49]JeckWR, SharplessNE, 2014. Detecting and characterizing circular RNAs. Nat Biotechnol, 32(5):453-461.

[50]JeckWR, SorrentinoJA, WangK, et al., 2013. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA, 19(2):141-157.

[51]JiangZY, ZhongZT, MiaoQQ, et al., 2021. circPTPN22 as a novel biomarker and ceRNA in peripheral blood mononuclear cells of rheumatoid arthritis. Mol Med Rep, 24(2):617.

[52]JinD, WuXW, YuHW, et al., 2018. Systematic analysis of lncRNAs, mRNAs, circRNAs and miRNAs in patients with postmenopausal osteoporosis. Am J Transl Res, 10(5):1498-1510.

[53]KongDL, GuR, ZhangCT, et al., 2020. Knockdown of hsa_circ_0059955 induces apoptosis and cell cycle arrest in nucleus pulposus cells via inhibiting itchy E3 ubiquitin protein ligase. Drug Des Devel Ther, 14:‍3951-3963.

[54]LiF, WuH, ZouGY, et al., 2021. Circular RNA_0062582 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells via regulation of microRNA-145/CBFB axis. Bioengineered, 12(1):1952-1963.

[55]LiHB, LanM, LiaoXG, et al., 2020. Circular RNA cir-ITCH promotes osteosarcoma migration and invasion through cir-ITCH/miR-7/EGFR pathway. Technol Cancer Res Treat, 19:1533033819898728.

[56]LiSL, PeiY, WangW, et al., 2019. Circular RNA 0001785 regulates the pathogenesis of osteosarcoma as a ceRNA by sponging miR-1200 to upregulate HOXB2. Cell Cycle, 18(11):1281-1291.

[57]LiTT, ZhangSH, YANGYX, et al., 2022. Co-regulation of circadian clock genes and microRNAs in bone metabolism. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(7):529-546.

[58]LiX, QuMT, ZhangJ, et al., 2021. CircASH2L facilitates tumor-like biologic behaviours and inflammation of fibroblast-like synoviocytes via miR-129-5p/HIPK2 axis in rheumatoid arthritis. J Orthop Surg Res, 16:302.

[59]LiYJ, PanDY, LiuS, et al., 2021. Identification of circ-FAM169A sponges miR-583 involved in the regulation of intervertebral disc degeneration. J Orthop Translat, 26:121-131.

[60]LiZ, ChenX, XuDR, et al., 2019. Circular RNAs in nucleus pulposus cell function and intervertebral disc degeneration. Cell Prolif, 52(6):e12704.

[61]LiZY, HuangC, BaoC, et al., 2015. Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol, 22(3):256-264.

[62]LiuF, WangYL, WeiJM, et al., 2021. Upregulation of circ_0000142 promotes multiple myeloma progression by adsorbing miR-610 and upregulating AKT3 expression. J Biochem, 169(3):327-336.

[63]LiuJH, DuF, ChenCH, et al., 2020. CircRNA ITCH increases bortezomib sensitivity through regulating the miR-615-3p/PRKCD axis in multiple myeloma. Life Sci, 262:118506.

[64]LiuQ, ZhangX, HuXQ, et al., 2016. Circular RNA related to the chondrocyte ECM regulates MMP13 expression by functioning as a miR-136 'sponge' in human cartilage degradation. Sci Rep, 6:22572.

[65]LiuX, TangH, LiuJ, et al., 2020. hsa_circRNA_101237: a novel diagnostic and prognostic biomarker and potential therapeutic target for multiple myeloma. Cancer Manag Res, 12:2109-2118.

[66]LiuZC, LiCW, HuangP, et al., 2020. CircHmbox1 targeting miRNA-1247-5p is involved in the regulation of bone metabolism by TNF-‍αin postmenopausal osteoporosis. Front Cell Dev Biol, 8:594785.

[67]LongZS, GongFP, LiYX, et al., 2020. Circ_0000285 regulates proliferation, migration, invasion and apoptosis of osteosarcoma by miR-409-3p/IGFBP3 axis. Cancer Cell Int, 20:481.

[68]LopesSM, RonconS, BordaloF, et al., 2020. Stem cells out of the bag: characterization of ex vivo expanded mesenchymal stromal cells for possible clinical use. Future Sci OA, 6(3):FSO449.

[69]LuoQ, ZhangL, LiX, et al., 2018. Identification of circular RNAs hsa_circ_0044235 in peripheral blood as novel biomarkers for rheumatoid arthritis. Clin Exp Immunol, 194(1):118-124.

[70]LuoQ, LiuJ, FuBQ, et al., 2019. Circular RNAs hsa_circ_0002715 and hsa_circ_0035197 in peripheral blood are novel potential biomarkers for new-onset rheumatoid arthritis. Dis Markers, 2019:2073139.

[71]LuoYH, ZhuXZ, HuangKW, et al., 2017. Emerging roles of circular RNA hsa_circ_0000064 in the proliferation and metastasis of lung cancer. Biomed Pharmacother, 96:‍‍892-898.

[72]LuoYW, GuiR, 2020. Circulating exosomal circMYC is associated with recurrence and bortezomib resistance in patients with multiple myeloma. Turk J Haematol, 37(4):248-262.

[73]LuoZH, ChenSJ, ChenXG, 2021. CircMAPK9 promotes the progression of fibroblast-like synoviocytes in rheumatoid arthritis via the miR-140-3p/PPM1A axis. J Orthop Surg Res, 16:395.

[74]MaWG, XueN, ZhangJH, et al., 2021. circUBAP2 regulates osteosarcoma progression via the miR-204-3p/HMGA2 axis. Int J Oncol, 58(3):298-311.

[75]MaXL, ZhuKP, ZhangCL, 2018. Circular RNA circ_HIPK3 is down-regulated and suppresses cell proliferation, migration and invasion in osteosarcoma. J Cancer, 9(10):1856-1862.

[76]MemczakS, JensM, ElefsiniotiA, et al., 2013. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature, 495(7441):333-338.

[77]MiaoF, YinBH, ZhangX, et al., 2020. CircRNA_009934 induces osteoclast bone resorption via silencing miR-5107. Eur Rev Med Pharmacol Sci, 24(14):7580-7588.

[78]NemtsovaMV, ZaletaevDV, BureIV, et al., 2019. Epigenetic changes in the pathogenesis of rheumatoid arthritis. Front Genet, 10:570.

[79]NiWY, JiangC, WuYZ, et al., 2021. CircSLC7A2 protects against osteoarthritis through inhibition of the miR-4498/TIMP3 axis. Cell Prolif, 54(6):e13047.

[80]QianDY, YanGB, BaiB, et al., 2017. Differential circRNA expression profiles during the BMP2-induced osteogenic differentiation of MC3T3-E1 cells. Biomed Pharmacother, 90:492-499.

[81]QuSB, YangXS, LiXL, et al., 2015. Circular RNA: a new star of noncoding RNAs. Cancer Lett, 365(2):141-148.

[82]QuW, JiangL, HouGH, 2021. Circ-AFF2/miR-650/CNP axis promotes proliferation, inflammatory response, migration, and invasion of rheumatoid arthritis synovial fibroblasts. J Orthop Surg Res, 16:165.

[83]RenW, YangL, DengT, et al., 2019. Calcitonin gene-related peptide regulates FOSL2 expression and cell proliferation of BMSCs via mmu_circRNA_003795. Mol Med Rep, 19(5):3732-3742.

[84]SalzmanJ, 2016. Circular RNA expression: its potential regulation and function. Trends Genet, 32(5):309-316.

[85]SalzmanJ, GawadC, WangPL, et al., 2012. Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS ONE, 7(2):e30733.

[86]SandellLJ, AignerT, 2001. Articular cartilage and changes in arthritis: cell biology of osteoarthritis. Arthritis Res Ther, 3(2):107.

[87]SangerHL, KlotzG, RiesnerD, et al., 1976. Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proc Natl Acad Sci USA, 73(11):3852-3856.

[88]ShenPY, YangYT, LiuG, et al., 2020. CircCDK14 protects against osteoarthritis by sponging miR-125a-5p and promoting the expression of Smad2. Theranostics, 10(20):9113-9131.

[89]ShiL, ZhangHL, SunJM, et al., 2022. CircSEC24A promotes IL-1β‍-induced apoptosis and inflammation in chondrocytes by regulating miR-142-5p/SOX5 axis. Biotechnol Appl Biochem, 69(2):701-713.

[90]SongJ, WangHL, SongKH, et al., 2018. CircularRNA_104670 plays a critical role in intervertebral disc degeneration by functioning as a ceRNA. Exp Mol Med, 50(8):1-12.

[91]SongY, HuN, SongXW, et al., 2020. Hsa_circ_0007841 enhances multiple myeloma chemotherapy resistance through upregulating ABCG2. Technol Cancer Res Treat, 19:1533033820928371.

[92]SueharaY, AlexD, BowmanA, et al., 2019. Clinical genomic sequencing of pediatric and adult osteosarcoma reveals distinct molecular subsets with potentially targetable alterations. Clin Cancer Res, 25(21):6346-6356.

[93]TaheriM, EghtedarianR, DingerME, et al., 2020. Dysregulation of non-coding RNAs in rheumatoid arthritis. Biomed Pharmacother, 130:110617.

[94]TianF, YuCT, YeWD, et al., 2017. Cinnamaldehyde induces cell apoptosis mediated by a novel circular RNA hsa_circ_0043256 in non-small cell lung cancer. Biochem Biophys Res Commun, 493(3):1260-1266.

[95]van RossumD, VerheijenBM, PasterkampRJ, 2016. Circular RNAs: novel regulators of neuronal development. Front Mol Neurosci, 9:74.

[96]VenøMT, HansenTB, VenøST, et al., 2015. Spatio-temporal regulation of circular RNA expression during porcine embryonic brain development. Genome Biol, 16:245.

[97]WanL, ZhangL, FanK, et al., 2016. Circular RNA-ITCH suppresses lung cancer proliferation via inhibiting the Wnt/β‍-catenin pathway. Biomed Res Int, 2016:1579490.

[98]WangHB, ZhuYK, CaoL, et al., 2021. circARL15 plays a critical role in intervertebral disc degeneration by modulating miR-431-5p/DISC1. Front Genet, 12:669598.

[99]WangQS, LuoSM, YangJ, et al., 2021. Circ_0114876 promoted IL-‍1β‍-induced chondrocyte injury by targeting miR-671/TRAF2 axis. Biotechnol Lett, 43(4):791-802.

[100]WangTF, HaoZY, LiuCC, et al., 2020. LEF1 mediates osteoarthritis progression through circRNF121/miR-665/MYD88 axis via NF-κB signaling pathway. Cell Death Discov, 11(7):598.

[101]WangXB, WangB, ZouMX, et al., 2018. CircSEMA4B targets miR-431 modulating IL-‍1β‍-induced degradative changes in nucleus pulposus cells in intervertebral disc degeneration via Wnt pathway. Biochim Biophys Acta (BBA) Mol Basis Dis, 1864(11):3754-3768.

[102]WangY, LinQD, SongCG, et al., 2020a. Circ_0007841 promotes the progression of multiple myeloma through targeting miR-338-3p/BRD4 signaling cascade. Cancer Cell Int, 20:383.

[103]WangY, LinQD, SongCG, et al., 2020b. Depletion of circ_0007841 inhibits multiple myeloma development and BTZ resistance via miR-129-5p/JAG1 axis. Cell Cycle, 19(23):3289-3302.

[104]WenJ, GuanZP, YuBS, et al., 2020. Circular RNA hsa_circ_0076906 competes with OGN for miR-1305 biding site to alleviate the progression of osteoporosis. Int J Biochem Cell Biol, 122:105719.

[105]WenJT, LiuJ, WangX, et al., 2021. Expression and clinical significance of circular RNAs related to immunity and inflammation in patients with rheumatoid arthritis. Int Immunopharmacol, 92:107366.

[106]WenJY, LiaoJY, LiangJN, et al., 2020. Circular RNA HIPK3: a key circular RNA in a variety of human cancers. Front Oncol, 10:773.

[107]WenY, LiB, HeM, et al., 2021. circHIPK3 promotes proliferation and migration and invasion via regulation of miR‑637/HDAC4 signaling in osteosarcoma cells. Oncol Rep, 45(1):169-179.

[108]WuCJ, ZhengZC, RenW, et al., 2018. Mm9_circ_009056 enhances osteogenesis by targeting BMP7 via CGRP-mediated miR-22-3p. Biochem Biophys Res Commun, 501(1):199-205.

[109]WuHJ, LiWH, ZhuST, et al., 2020. Circular RNA circUBAP2 regulates proliferation and invasion of osteosarcoma cells through miR-641/YAP1 axis. Cancer Cell Int, 20:223.

[110]WuY, ZhangY, ZhangY, et al., 2017. CircRNA hsa_circ_0005105 upregulates NAMPT expression and promotes chondrocyte extracellular matrix degradation by sponging miR-26a. Cell Biol Int, 41(12):1283-1289.

[111]WuYZ, HongZH, XuWB, et al., 2021. Circular RNA circPDE4D protects against osteoarthritis by binding to miR-103a-3p and regulating FGF18. Mol Ther, 29(1):308-323.

[112]XiangQ, KangL, WangJT, et al., 2020. CircRNA-CIDN miti

[113]gated compression loading-induced damage in human nucleus pulposus cells via miR-34a-5p/SIRT1 axis. eBioMedicine, 53:102679.

[114]XieL, HuangWB, FangZH, et al., 2019. CircERCC2 ameliorated intervertebral disc degeneration by regulating mitophagy and apoptosis through miR-182-5p/SIRT1 axis. Cell Death Discov, 10(10):751.

[115]XuGY, LiuC, JiangJ, et al., 2020. A novel mechanism of intervertebral disc degeneration: imbalance between autophagy and apoptosis. Epigenomics, 12(13):1095-1108.

[116]XuZH, HeJ, ZhouXD, et al., 2020. Down-regulation of LECT2 promotes osteogenic differentiation of MSCs via activating Wnt/β‍-catenin pathway. Biomed Pharmacother, 130:110593.

[117]YamadaKM, ArakiM, 2001. Tumor suppressor PTEN: modulator of cell signaling, growth, migration and apoptosis. J Cell Sci, 114(Pt 13):2375-2382.

[118]YamaguchiA, KomoriT, SudaT, 2000. Regulation of osteoblast differentiation mediated by bone morphogenetic proteins, hedgehogs, and Cbfa1. Endocr Rev, 21(4):‍393-411.

[119]YaoT, YangYT, XieZA, et al., 2021. Circ0083429 regulates osteoarthritis progression via the miR-346/SMAD3 axis. Front Cell Dev Biol, 8:579945.

[120]YiXH, ZhangB, FuYR, et al., 2020. STAT1 and its related molecules as potential biomarkers in Mycobacterium tuberculosis infection. J Cell Mol Med, 24(5):2866-2878.

[121]YouXT, VlatkovicI, BabicA, et al., 2015. Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity. Nat Neurosci, 18(4):603-610.

[122]YuJZ, YangMJ, ZhouB, et al., 2019. CircRNA-104718 acts as competing endogenous RNA and promotes hepatocellular carcinoma progression through microRNA-218-5p/TXNDC5 signaling pathway. Clin Sci, 133(13):1487-1503.

[123]YuL, LiuYG, 2019. circRNA_0016624 could sponge miR-98 to regulate BMP2 expression in postmenopausal osteoporosis. Biochem Biophys Res Commun, 516(2):‍546-550.

[124]YuanDM, MaJ, FangWB, 2019. Identification of non-coding RNA regulatory networks in pediatric acute myeloid leukemia reveals circ-0004136 could promote cell proliferation by sponging miR-142. Eur Rev Med Pharmacol Sci, 23(21):9251-9258.

[125]YuanXF, ZhangYC, CaiC, et al., 2021. Circular RNA circZNF652 is overexpressed in osteoarthritis and positively regulates LPS-induced apoptosis of chondrocytes by upregulating PTEN. Autoimmunity, 54(7):415-421.

[126]ZangJK, LuD, XuAD, 2020. The interaction of circRNAs and RNA binding proteins: an important part of circRNA maintenance and function. J Neurosci Res, 98(1):87-97.

[127]ZhaiNX, LuYQ, WangYZ, et al., 2018. Circular RNAs and hereditary bone diseases. Intractable Rare Dis Res, 7(1):1-6.

[128]ZhangF, LinFL, XuZW, et al., 2021. Circular RNA ITCH promotes extracellular matrix degradation via activating Wnt/β‍-catenin signaling in intervertebral disc degeneration. Aging, 13(10):14185-14197.

[129]ZhangH, WangGC, DingC, et al., 2017. Increased circular RNA UBAP2 acts as a sponge of miR-143 to promote osteosarcoma progression. Oncotarget, 8(37):61687-61697.

[130]ZhangM, MouLM, LiuSW, et al., 2021. Circ_0001103 alleviates IL-‍1β‍-induced chondrocyte cell injuries by upregulating SIRT1 via targeting miR-375. Clin Immunol, 227:108718.

[131]ZhangY, ZhangXO, ChenT, et al., 2013. Circular intronic long noncoding RNAs. Mol Cell, 51(6):792-806.

[132]ZhangY, XueW, LiX, et al., 2016. The biogenesis of nascent circular RNAs. Cell Rep, 15(3):611-624.

[133]ZhangYL, LiuQF, LiaoQ, 2020. CircHIPK3: a promising cancer-related circular RNA. Am J Transl Res, 12(10):6694-6704.

[134]ZhangZC, PuFF, WangBC, et al., 2020. Hsa_circ_0000285 functions as a competitive endogenous RNA to promote osteosarcoma progression by sponging hsa-miRNA-599. Gene Ther, 27(5):186-195.

[135]ZhangZR, YangTT, XiaoJJ, 2018. Circular RNAs: promising biomarkers for human diseases. eBioMedicine, 34:‍267-274.

[136]ZhaoW, ChuSS, JiaoYQ, 2019. Present scenario of circular RNAs (circRNAs) in plants. Front Plant Sci, 10:379.

[137]ZhaoY, ZhangBZ, ZhangQQ, et al., 2021. Tumor-associated macrophages in osteosarcoma. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 22(11):885-892.

[138]ZhengFP, YuXQ, HuangJH, et al., 2017. Circular RNA expression profiles of peripheral blood mononuclear cells in rheumatoid arthritis patients, based on microarray chip technology. Mol Med Rep, 16(6):8029-8036.

[139]ZhiLQ, LiangJQ, HuangW, et al., 2021. Circ_AFF2 facilitates proliferation and inflammatory response of fibroblast-like synoviocytes in rheumatoid arthritis via the miR-375/TAB2 axis. Exp Mol Pathol, 119:104617.

[140]ZhongSP, OuyangQQ, ZhuDJ, et al., 2020. Hsa_circ_0088036 promotes the proliferation and migration of fibroblast-like synoviocytes by sponging miR-140-3p and upregulating SIRT 1 expression in rheumatoid arthritis. Mol Immunol, 125:131-139.

[141]ZhouF, WangDJ, WeiW, et al., 2020. Comprehensive profiling of circular RNA expressions reveals potential diagnostic and prognostic biomarkers in multiple myeloma. BMC Cancer, 20:40.

[142]ZhouW, LiuY, WuXJ, 2021. Down-regulation of circITCH promotes osteosarcoma development and resistance to doxorubicin via the miR-524/RASSF6 axis. J Gene Med, 23(10):e3373.

[143]ZhouZB, HuangGX, FuQ, et al., 2019. circRNA.33186 contributes to the pathogenesis of osteoarthritis by sponging miR-127-5p. Mol Ther, 27(3):531-541.

[144]ZhouZB, MaJ, LuJJ, et al., 2021. Circular RNA CircCDH13 contributes to the pathogenesis of osteoarthritis via CircCDH13/miR-296-3p/PTEN axis. J Cell Physiol, 236(5):3521-3535.

[145]ZhuK, NiuL, WangJ, et al., 2019. Circular RNA hsa_circ_0000885 levels are increased in tissue and serum samples from patients with osteosarcoma. Med Sci Monit, 25:1499-1505.

[146]ZuoL, ZhangL, ZuJ, et al., 2020. Circulating circular RNAs as biomarkers for the diagnosis and prediction of outcomes in acute ischemic stroke. Stroke, 51(1):319-323.

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